2-29071387-C-T

Position:

chr2-29071387-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001029883.3(PCARE):c.2875G>A(p.Ala959Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,613,724 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 47 hom. )

Consequence

PCARE
NM_001029883.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.679

Variant links:

Genes affected

PCARE (HGNC:34383): (photoreceptor cilium actin regulator) The protein encoded by this gene is highly expressed in photoreceptors and may associate with the primary cilium of the outer segment. The encoded protein appears to undergo post-translational lipid modification. Nonsense and missense variants of this gene appear to cause a recessive form of retinitis pigmentosa. [provided by RefSeq, Jun 2010]

PCARE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031301677).

BP6

Variant 2-29071387-C-T is Benign according to our data. Variant chr2-29071387-C-T is described in ClinVar as [Benign]. Clinvar id is 193141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-29071387-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00173 (263/152318) while in subpopulation SAS AF= 0.0112 (54/4832). AF 95% confidence interval is 0.0088. There are 4 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCARE	NM_001029883.3 linkuse as main transcript	c.2875G>A	p.Ala959Thr	missense_variant	1/2	ENST00000331664.6	NP_001025054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCARE	ENST00000331664.6 linkuse as main transcript	c.2875G>A	p.Ala959Thr	missense_variant	1/2	2	NM_001029883.3	ENSP00000332809.4		A6NGG8

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

263

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00413

AC:

1027

AN:

248692

Hom.:

AF XY:

0.00464

AC XY:

627

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0412

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00810

GnomAD4 exome

AF:

0.00220

AC:

3210

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1880

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152318

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00301

Hom.:

Bravo

AF:

0.00187

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00299

AC:

ExAC

AF:

0.00365

AC:

442

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 07, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 54

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 26, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Aug 11, 2016	- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

DANN

Benign

0.92

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.35

REVEL

Benign

0.032

Sift

Benign

0.21

Sift4G

Uncertain

0.042

Polyphen

0.0

Vest4

0.025

MVP

0.076

MPC

0.013

ClinPred

0.0012

GERP RS

-1.3

Varity_R

0.035

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over